This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. EcoP15I is a type III restriction endonuclease that requires two inversely oriented recognition sites to cut a DNA at specific distance. This enzyme contains two polypeptides [unreadable]a modification (Mod) subunit or methyl transferase and a restriction subunit (Res). EcoP15I (M.W. ~ 380 kDa) exists as a hetero-tetramer in a Mod2-Res2 arrangement. EcoP15I exhibits an ATP driven translocase activity to communicate between two sites spaced as far as 3500 bp apart and efficiently cleaves 25 bp away from the recognition site on the top strand and 27 bp away on the bottom strand. The crystal structure of this enzyme would be the first of the type III enzyme and would shed light on the mechanism by which type III restriction endonucleases cleave the DNA at specific distance. We have succeeded first time in cocrystallizing this enzyme in its native form. The cocrystals belong to the space group P4122 with unit cell parameters a=b=105?, c=578? and ?=?=?=90[unreadable]. The asymmetric unit contains one hetrotetramer. These crystals diffract weakly to ~6? at home source and ~4? on other beamlines. Given the fact that one unit cell axis is very large (578?). In order to get better diffraction and to resolve the issues with such a large unit cell, we need an access to a better beamline such as X29.